Department of Biochemistry
School of Medicine & Biomedical Sciences
Faculty
CHRISTINE CAMPBELL, Ph.D.
Research Assistant Professor
- email: cc59@buffalo.edu
T-Box Genes and Development
My laboratory is interested in the biochemical and developmental role of a family of transcriptional regulatory proteins called T-box proteins. T-box proteins are a highly evolutionarily conserved family of sequence specific DNA binding proteins that are present in all metazoa. There are seventeen known vertebrate T-box genes that exhibit unique but overlapping expression patterns during embryogenesis. Gene knockouts or naturally occurring human mutations have been described for ten of them. The majority of these mutations are associated with specific phenotypic effects in heterozygotes and are embryonic lethals in homozygotes.
As I have a long-standing interest in kidney development, I am particularly interested in the role of T-box genes in this organ. Although none of the T-box gene mutations described to date are associated with kidney defects, we have identified at least six different T-box genes that are expressed in the kidney (Tbx1, Tbx2, Tbx3, Tbx20 and Tbx22). We have shown using a transient transfection assay that Tbx2, Tbx3 and Tbx20 all function as transcriptional repressors in human embryonic kidney 293 cells while Tbx1 has no effect. However, long term overexpression of Tbx2 or Tbx3 is toxic in these cells while overexpression of Tbx20 is not. Work in the laboratory is currently focused on gene chip analysis of 293 cells expressing each of these proteins with the aim of identifying downstream target genes. Although most of the T-box proteins we have tested to date modulate the transcriptional activity of our reporter construct, we hypothesize that each T-box protein will have unique endogenous targets.
A fourth T-box gene being studied in the laboratory is T-bet. This gene product is produced primarily in a subset of cytotoxic or helper T cells that express type I cytokines. We are currently studying T-bet expression in T cells from patients with renal cell carcinoma to determine whether the T cell defects manifested by many of these patients include alterations in T-bet expression or function. In addition we are looking to overexpress T-bet in non-hematopoetic cells to determine whether the ability of T-bet to induce gene expression in T-cells requires other T-cell specific factors.
Selected Recent Publications
Sinha S, Abraham S, Gronostajski RM and CE Campbell. (2000) Differential DNA binding and transcription modulation by three T-box proteins T, TBX1 and TBX2. Gene 258: 15-29.
He M, Wen L, Campbell CE, Wu JY and Y Rao (1999) Transcription Repression by Xenopus ET and Its Human Ortholog TBX3, a Gene Involved in Ulnar-Mammary Syndrome. Proc. Natl. Acad. Sci. USA 96: 10212-10217
Bamshad M, Le T, Watkins WS, Dixon ME, Kramer BE, Roeder AD, Carey JC, Root S, Schinzel A, Van Maldergem L, Gardner M, Lin RC, Seidman CE, Seidman JG, Wallerstein R, Moran E, Sutphen R, Campbell CE and LB Jorde (1999) The spectrum of mutations in TBX3: genotype/phenotype relationship in ulnar-mammary syndrome. Am. J. Hum. Genet. 64: 1550-1562.
Campbell CE, Casey G, and K Goodrich (1998) Genomic Structure of TBX2 indicates conservation of with distantly Related T-Box Genes. Mammalian Genome 9: 70-73.
Campbell CE, Goodrich K, Casey G and B. Beatty (1995) Cloning and mapping of a human gene (TBX2) sharing a highly conserved protein motif with the drosophila omb gene. Genomics 28: 255-260.
Return
to Faculty Page
BCH Home
UB Home